The main immunoglobulin (Ig) in human blood is IgG. This is the second most abundant circulating protein and contains long-term protective antibodies against many infectious agents. IgG is a combination of four slightly different types of IgG called IgG subclasses: IgG1, IgG2, IgG3 and IgG4. When one or more of these subclasses is persistently low and total IgG is normal, a subclass deficiency is present. Although this deficiency may occasionally explain a patient’s problems with infections, IgG subclass deficiency is a controversial diagnosis and experts disagree about the importance of this finding as a cause of repeated infections.
A common misdiagnosis:
The misdiagnosis of IgG subclass deficiency as a cause of presumed immunodeficiency is common, often leading to unnecessary long-term use of Ig replacement therapy. A subclass deficiency needs to be considered and looked for only under special circumstances discussed in this chapter.
Different functions of IgG subclasses:
While all the IgG subclasses contain antibodies to components of many disease-causing bacteria and viruses, each subclass serves a slightly different function in protecting the body against infection. For example, IgG1 and IgG3 subclasses are rich in antibodies against proteins such as the toxins produced by the diphtheria and tetanus bacteria, as well as antibodies against viral proteins. In contrast, IgG2 antibodies are predominantly against the polysaccharide (complex sugar) coating (capsule) of certain disease-producing bacteria (such as, Streptococcus pneumoniaeand Haemophilus influenzae).
More details on IgG subclass deficiencies:
The normal IgG breakdown in the bloodstream is:
- 60-70% IgG1,
- 20-30% IgG2,
- 5-8% IgG3
- 1-3% IgG4
IgG subclass deficiencies affect only IgG subclasses (usually IgG2 or IgG3), with normal total IgG and IgM immunoglobulins and other components of the immune system being at normal levels. These deficiencies can affect only one subclass or involve an association of two subclasses, such as IgG2 and IgG4.
IgG2 or IgG3 deficiencies are the most common IgG subclass deficiencies. Since IgG1 comprises 60% of the total IgG level, deficiency of IgG1 usually drops the total IgG level below the normal range, resulting in hypogammaglobulinemia.
IgG subclass levels are age-dependent:
The amount of the different IgG subclasses present in the bloodstream varies with age. For example, IgG1 and IgG3 reach normal adult levels by 5-7 years of age while IgG2 and IgG4 levels rise more slowly, reaching adult levels at about 10 years of age. In young children, the ability to make IgG2 antibodies to the polysaccharide coatings of bacteria develops more slowly than the ability to make antibodies to proteins.
Sources:
Elevated IgG subclass 2 levels can indicate a variety of underlying conditions and may have different implications depending on the clinical context. To provide a comprehensive understanding, let's delve into the immunoglobulin G (IgG) subclasses, their functions, potential causes for elevation, associated conditions, diagnostic approaches, and possible treatment options.
Understanding IgG and Its Subclasses:
Immunoglobulin G (IgG) is the most abundant type of antibody in the blood and extracellular fluid, playing a crucial role in the body's immune response against infections. IgG is divided into four subclasses: IgG1, IgG2, IgG3, and IgG4, each with distinct functions and distributions.
→ IgG1: Predominantly involved in responses to protein antigens.
→ IgG2: Primarily responds to polysaccharide antigens and is important in the defense against bacterial infections.
→ IgG3: Known for its ability to activate complement and is involved in responses to protein antigens.
→ IgG4: Generally associated with chronic exposure to antigens and has a role in allergy and tolerance mechanisms.
Elevated IgG Subclass 2 Levels:
When IgG subclass 2 levels are elevated, it suggests an abnormal immune response, which can be caused by various factors.
Potential Causes and Associated Conditions:
→ Chronic Infections:
→ Autoimmune Diseases:
→ Allergic Reactions:
→ Immunodeficiency Disorders:
→ Chronic Inflammatory Conditions:
Diagnostic Evaluation:
When elevated IgG2 levels are detected, a thorough diagnostic workup is essential to determine the underlying cause:
Clinical History and Physical Examination:
Laboratory Tests:
Immunological Tests:
Treatment Options:
Treatment for elevated IgG2 levels focuses on addressing the underlying cause:
Infections:
Autoimmune Diseases:
Allergies:
Immunodeficiency Disorders:
Chronic Inflammatory Conditions:
Elevated IgG subclass 2 levels can be a marker of various underlying conditions, including chronic infections, autoimmune diseases, allergies, immunodeficiency disorders, and chronic inflammatory conditions. A comprehensive diagnostic approach is essential to identify the underlying cause, and treatment should be tailored accordingly. Managing the underlying condition often leads to normalization of IgG2 levels and improved patient outcomes. If you or someone you know has elevated IgG2 levels, consulting a healthcare provider specializing in immunology or infectious diseases is recommended for a detailed evaluation and appropriate management.
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- People with persistently low levels of one or two IgG subclasses and a normal total IgG level have a selective IgG subclass deficiency.
- People with IgG subclass deficiency require more extensive diagnostic evaluation including the demonstration of a poor antibody response to vaccine challenge before one is diagnosed with a clinically significant IgG subclass deficiency necessitating specific treatment that may include Ig replacement therapy.
- IgG subclass deficiencies may be associated with other immunoglobulin abnormalities. One common pattern is IgG2 and IgG4 subclass deficiency associated with IgA deficiency.
- IgG subclass deficiencies are also an integral component of other well-known primary immunodeficiency diseases, such as Wiskott-Aldrich Syndrome and Ataxia-Telangiectasia.
- IgG subclass deficiencies are sometimes associated with poor or partial responses to pneumococcal polysaccharides, specifically IgG2 deficiency with or without IgG4 deficiency.
IgG1 deficiency:
Selective IgG1 deficiency is very rare, as it is usually associated with deficiency of either IgG3, or other immunoglobulin classes, such as in common variable immunodeficiency. Isolated IgG1 deficiency has been reported in chronic fatigue syndrome. As IgG1 is the most abundant IgG subclass, its deficiency often results in hypogammaglobulinemia.
IgG1 and IgG3 deficiency:
People with this combination are commonly present with infections of the lower airways, which can progress to chronic lung disease.
IgG2 and IgG4 deficiency:
Conversely, IgG2 and IgG4 deficiencies manifest in the form of otitis media and sinusitis. IgG2 deficiency is the most common type of IgG subclass deficiency, either as an isolated finding or together with IgG4 deficiency. People with this defect have recurrent infections with encapsulated bacteria such as Streptococcus pneumonia and/or Haemophilus influenza type B. IgG2 deficiency often results in infectious complications, such as bronchiectasis, bronchopneumonia, bronchitis, obstructive lung disease, and asthma. It has also been associated with ataxia telangiectasia and systemic lupus erythematosus (SLE). Children with SLE and IgG2 and IgG4 deficiency may present with cardiac tamponade, instead of the more common nephropathy and arthritis. The impact of decreased concentration of IgG4 cannot be easily assessed, since IgG4 may be present in low concentrations in healthy children. Nevertheless, it was shown that low concentrations of IgG4 are present in a large percentage of patients with recurrent respiratory tract infections.
Possible symptoms:
People with any form of IgG subclass deficiency occasionally suffer from recurrent respiratory infections similar to the ones seen in other antibody deficiency syndromes, chiefly infections with encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. An increased frequency of viral upper respiratory infections may not be an indication of antibody deficiency. Therefore, it is critical to distinguish between infections caused by respiratory viruses from those due to bacterial pathogens.
A few people with IgG subclass deficiency may appear very similar to patients with severe immunoglobulin deficiencies. Rarely, IgG subclass deficient patients may have recurrent episodes of bacterial meningitis or infections of the bloodstream (sepsis).
Diagnosis:
The finding of an IgG subclass deficiency should prompt reevaluation over a period of months before determining that the patient is truly immunodeficient. Subclass deficiencies need to be carefully interpreted taking into account the clinical status of the patient as well as the person’s ability to produce specific antibodies in response to vaccines.
Measurement of IgG subclasses can be recommended in the presence of known associated abnormalities, particularly if recurrent infections are also present.
These circumstances include:
- IgA deficient patients with recurrent infections to determine if there is an associated IgG2 and IgG4 subclass deficiency
- Wiskott-Aldrich and Ataxia-Telangiectasia patients at the onset of recurrent infections
- Specific Antibody Deficiency patients with normal total immunoglobulins
Possible treatment:
- Recurrent or chronic infections of the ears, sinuses and lungs need comprehensive treatment to prevent permanent damage that might result in hearing loss or chronic lung disease. It is also important to encourage patients to continue normal activities of daily living, such as school or work.
- The mainstay of treatment includes appropriate use of antibiotics to treat and prevent infections. The type and severity of infection usually determines the type of antibiotic used and the length of treatment.
- Ig therapy is an option for selected symptomatic patients that have persistent IgG subclass deficiencies, documented poor responses to polysaccharide vaccines and who fail prophylactic antibiotic therapy. The decision to begin Ig replacement therapy needs to be carefully discussed with the healthcare provider
- People with frequent infections and persistent IgG subclass deficiencies with normal anti-polysaccharide antibodies should also be treated using adequate prevention, vaccine and antibiotic therapy, perhaps even considering the use of Ig replacement if other treatment fails.
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See your lab reports in clear graphs and tables. Spot patterns, track changes, and compare results over time — all in one place.
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Our inclusive service handles the data entry for your lab reports. Just submit your information and we'll take care of the rest.
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
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Healthmatters is a personal health dashboard that helps you organize and understand your lab results. It collects and displays your medical test data from any lab in one secure, easy-to-use platform.
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You can combine all test reports inside your Healthmatters account and keep them in one place. It gives you an excellent overview of all your health data. Once you retest, you can add new results and compare them.
If you are still determining whether Healthmatters support your lab results, the rule is that if you can test it, you can upload it to Healthmatters.
While we work with many popular labs, we welcome reports from lots of other places too.
It's as simple as this: if you can get a test done, you can upload it to Healthmatters and we can interpret results from any lab out there. If laboratories can analyze it, we can interpret it.
If you're on the hunt for a specific biomarker, contact us and we'll add it to our database. Anything from blood, urine, saliva, or stool can be uploaded, understood, and tracked with your Healthmatters account.
The Complete Plan ($15/month) is perfect for individuals who want ongoing access to their health data. It includes unlimited lab imports, visual tracking, custom ranges, result explanations, full account exports, and secure sharing — all with a simple monthly subscription. You can cancel anytime and restart your plan whenever you're ready — your data will still be there waiting for you. You can also upgrade to the Unlimited Plan at any time, with the cost prorated based on what you've already paid.
The Unlimited Plan ($250 one-time) is also designed for individuals but offers lifetime access with no ongoing subscription. You'll get all the same features as the Complete Plan, plus a larger initial data entry allowance (10 reports), making it a great choice if you prefer a one-time payment and long-term use without monthly fees.
In short:
There are two ways to add your test reports to your Healthmatters account. One option is to input the data using the data entry forms. The other method is to utilize our "Data entry service."
Our data entry forms offer an easy, fast, and free way for you to input the reports yourself. Self-entry allows you to add an unlimited number of reports at no cost. We make the self-entry process user-friendly, providing dozens of templates that pre-populate the most popular laboratory panels and offering instant feedback on entered values.
For those who prefer assistance, we offer a "Data entry service" to help you input your data. Simply attach an image or file of your lab test results, and a qualified team member from our data entry team will add the results for you.
We support various file types, including PDFs, JPGs, or Excel. This service is particularly useful if you have many reports to upload or if you're too busy to handle the data entry yourself.
Our Data Entry Service is for when you don't want to manually type in your lab results yourself. You simply upload your report (PDF, image, or screenshot), and our trained team enters the information into your Healthmatters account for you — accurately and neatly organized, ready to view in graphs, tables, and timelines.
The $15 per report covers the time and care it takes for a real person to review your file, make sure each result is entered correctly, and double-check for accuracy. This ensures your health data is precise and easy to work with — without you having to spend the time doing it yourself.
Prefer to do it yourself? You can always use our free self-entry tool to add results manually — it just takes a bit more time and attention.
For users on the Complete monthly plan, the first report is entered free of charge, and each additional report incurs a fee of $15.
Unlimited account holders enjoy the entry of ten reports without charge. Subsequent reports are subject to a $15 fee per report.
Additionally, users on the Complete plan can upgrade to a yearly subscription from the account settings. The annual subscription includes a data entry service for five reports.
All professional accounts allow you to import and onboard an unlimited number of clients and their lab results. The distinction between professional plans lies solely in the data entry service.
The Pro Monthly Plus plan is priced at $75 per month and includes a data entry service for five reports each month. Additional reports can be self-entered at no extra cost or, if preferred, you can use our data entry service for an additional fee of $15 per report.
The Pro Monthly plan is priced at $45 per month and does not include a data entry service. Self-entry is free for an unlimited number of reports, and you can opt for the data entry service at a fee of $15 per report.
You also have the option to upgrade to higher monthly or to annual plans, which come with substantial discounts. All upgrades can be done directly from your account.
Simply log in and navigate to your account settings to cancel your subscription. Scroll down to locate the 'Cancel' button at the bottom of the page. Ensure you cancel at least one day before the renewal date to prevent any charges. Once cancellation is requested, the subscription remains active until the conclusion of the current billing cycle.
Our goal has been to make your Healthmatters account as intuitive as possible.
We've crafted multiple ways for you to navigate your data, whether you're glancing at a single report or delving into your historical test reports.
1. Graph View:Dive into a visual journey with our biomarker graphs, showcasing over 40 data points. Combining years of results unveils trends, empowering you to make informed decisions. Our visualization tools make it a breeze to compare and understand changes over time, even if your results are from different labs. A search function and filters simplify the exploration of extensive data, allowing you to focus on what needs attention.
2. All Tests ViewExplore neatly organized reports on a timeline, highlighting crucial details like dates, critical results, and lab/panel names. Each report opens up to reveal in-depth descriptions and additional recommendations for each biomarker. The history of previous results is just a click away, and you can download a comprehensive report for deeper insights. Color-coded and user-friendly, it's designed for easy reading, understanding, and navigation.
3. Table View:For a holistic view of all biomarkers side by side, our table view is your go-to. Results are neatly displayed in a categorized and dated table, ideal for those with an extensive test history. Utilize sorting, filters, and color-coding to enhance your analysis and gain extra insights.
Yes, you can download your information anytime. We offer two easy ways to export your lab data:
This makes it simple to save, back up, or share your health data whenever you need.
Yes, you can print your report. To do so, navigate to "All tests" and open the report you wish to print. You'll find a print button in the right corner of the report. Click on it, and your browser's print window will open. If you prefer to print in a bigger typeface, adjust the scale using the print window settings.
Yes, you can! We highly recommend activating Two-Factor Authentication (2FA) for your account. To do so, please navigate to the "Profile and Security" section of your account, where you will find instructions for activating 2FA.
Yes, you can. When entering values for the biomarker, you will see an "Edit Range" button. Click this button, and you'll have the option to enter a custom range.
A personal account is all about keeping your own lab test results in check. It's just for you and your personal use.
The professional account is designed for health professionals who wish to track and organize their clients' laboratory results.
To learn more about Healthmatters Pro, please refer to the professional page.
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Optimal Result:
241 - 700 mg/dL.